Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0013085
UniProt IDP22455
Primary gene name(s)FGFR4
Synonym gene name(s)JTK2, TKF
Protein nameFibroblast growth factor receptor 4
Protein functionTyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling. {ECO:0000269|PubMed:11433297, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:18670643, ECO:0000269|PubMed:20018895, ECO:0000269|PubMed:20683963, ECO:0000269|PubMed:20798051, ECO:0000269|PubMed:20876804, ECO:0000269|PubMed:21653700, ECO:0000269|PubMed:7518429, ECO:0000269|PubMed:7680645, ECO:0000269|PubMed:8663044}.
Subcellular locationCell membrane;
Single-pass type I membrane protein. Endosome. Endoplasmic reticulum. Note=Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane.;
SUBCELLULAR LOCATION: Isoform 2: Secreted.;
SUBCELLULAR LOCATION: Isoform 3: Cytoplasm {ECO:0000269|PubMed:11781352}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P22455
Gene Ontology
(Biological Process)
Complete annatation
cell migration [GO:0016477];
fibroblast growth factor receptor signaling pathway [GO:0008543];
glucose homeostasis [GO:0042593];
MAPK cascade [GO:0000165];
peptidyl-tyrosine phosphorylation [GO:0018108];
phosphate ion homeostasis [GO:0055062];
phosphatidylinositol-mediated signaling [GO:0048015];
positive regulation of catalytic activity [GO:0043085];
positive regulation of cell proliferation [GO:0008284];
positive regulation of DNA biosynthetic process [GO:2000573];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of gene expression [GO:0010628];
positive regulation of proteolysis [GO:0045862];
protein autophosphorylation [GO:0046777];
regulation of bile acid biosynthetic process [GO:0070857];
regulation of cholesterol homeostasis [GO:2000188];
regulation of extracellular matrix disassembly [GO:0010715];
regulation of lipid metabolic process [GO:0019216];
regulation of phosphatidylinositol 3-kinase signaling [GO:0014066]
Gene Ontology
(Molecular Function)
Complete annatation
1-phosphatidylinositol-3-kinase activity [GO:0016303];
ATP binding [GO:0005524];
fibroblast growth factor-activated receptor activity [GO:0005007];
fibroblast growth factor binding [GO:0017134];
heparin binding [GO:0008201];
phosphatidylinositol-4,5-bisphosphate 3-kinase activity [GO:0046934];
protein tyrosine kinase activity [GO:0004713];
Ras guanyl-nucleotide exchange factor activity [GO:0005088]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
endoplasmic reticulum [GO:0005783];
endosome [GO:0005768];
extracellular region [GO:0005576];
Golgi apparatus [GO:0005794];
integral component of plasma membrane [GO:0005887];
nucleoplasm [GO:0005654];
plasma membrane [GO:0005886];
transport vesicle [GO:0030133]
Protein-protein interaction108555
Phylogenetic treeP22455
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3unknownunknownunknown
AZA vs. DISU1.436191662624334.68457858882054e-060.00156922972550846
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD31.355123827720110.1222442202239080.218149565011862
DISU vs. IL7-2.006507356054853.98852062488686e-101.62505266000458e-07
DISU vs. SAHA-0.661114028823490.0475152106565440.271662268514709
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3unknownunknownunknown
DMSO vs. DISU-1.600819763413091.42266898039978e-076.6998817295702e-05
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activation0.2250018296461670.8917174349473450.999983755607037
HIV vs. Mock in Latencyunknownunknownunknown
IL7 vs. CD3unknownunknownunknown
SAHA vs. CD30.6850139240792070.4124759080762680.528033633597465
SAHA vs. IL7unknownunknownunknown
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
NOTEST -0.618714 1
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00039 Palifermin approved unknown unknown
DB08901 Ponatinib approved unknown inhibitor
DB09078 Lenvatinib approved yes Inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1QCT Model - B/E=36-353.
4QQ5 X-ray 2.2Å A=445-753.
4QQC X-ray 2.4Å A=445-753.
4QQJ X-ray 1.6Å A=445-753.
4QQT X-ray 1.5Å A=445-753.
4QRC X-ray 1.9Å A=445-753.
4R6V X-ray 2.3Å A=445-753.
4TYE X-ray 2.8Å A=447-753.
4TYG X-ray 2.4Å A=447-753.
4TYI X-ray 3.4Å A=447-753.
4TYJ X-ray 2.4Å A=447-753.
4UXQ X-ray 1.8Å A=447-753.
4XCU X-ray 1.7Å A=449-751.
5JKG X-ray 2.3Å A=445-753.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04015 Rap1 signaling pathway - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04550 Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
hsa04810 Regulation of actin cytoskeleton - Homo sapiens (human)